Cell-based assays for the detection of MOG antibodies: a comparative study

M. Gastaldi, S. Scaranzin, S. Jarius, B. Wildeman, E. Zardini, G. Mallucci, E. Rigoni, E. Vegezzi, T. Foiadelli, S. Savasta, P. Banfi, M. Versino, L. Benedetti, G. Novi, M.M. Mancardi, T. Giacomini, P. Annovazzi, D. Baroncini, D. Ferraro, V. LampasonaM. Reindl, P. Waters, D. Franciotta

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Background: The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the differential diagnosis of acquired demyelinating syndromes of the CNS, among which multiple sclerosis (MS). We compared the diagnostic performance of four cell-based assays (CBAs) for their detection. Methods: Consecutive sera from 204 patients with ‘possible MOGAD’ (55), MS (112), and other neurological disorders (OND, 37) were tested for MOG-IgG with a live-CBA with anti-heavy-and-light chain secondary-antibody (LCBA-IgGH+L), and a live-CBA for IgG1 (LCBA-IgG1). A subgroup of 71 patients was additionally tested with a live-CBA with anti-Fcγ secondary-antibody (LCBA-IgGFcγ), and a commercial fixed-CBA with anti-Fcγ secondary-antibody (FCBA-IgGFcγ). Results: Fifty-seven/204 patients (27.9%) were MOG-IgG-positive. Sensitivity was 89.1% (CI:77.8–95.9) and specificity 93.3% (CI:88.0–96.7) for LCBA-IgGH+L, and 74.6% (CI:61.0–85.3) and 100% (CI:97.6–100) for LCBA-IgG1. Eighteen of 57 (31%) samples showed discrepant results (all negative on LCBA-IgG1); of these, three with ‘possible MOGAD’ showed high-titer MOG-IgG (≥ 1:640), and positivity for MOG-IgG2, whereas 15/18 had low-titer MOG-IgG (1:160/1:320) and mixed diagnoses (5 ‘possible MOGAD’, 6 MS, 4 OND). In the subgroup analysis, sensitivity was 92.3% (CI:79.1–98.4) and specificity 97.0% (CI:83.8–99.9) for LCBA-IgGFcγ, and 87.2% (CI:72.6–95.7) and 97.0% (CI:83.8–99.9) for FCBA-IgGFcγ. Conclusions: LCBA-IgG1 showed the highest specificity but can miss MOG-IgG2 reactivities, whose meaning warrants further investigations. Titration of samples tested with LCBA-IgGH+L/ IgGFcγ is important for meaningful interpretation of the results. In the subgroup analysis, LCBA-IgGFcγ yielded the highest accuracy, and FCBA-IgGFcγ good specificity, but it was at risk of false-negative results. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Original languageEnglish
JournalJ. Neurol.
Publication statusPublished - 2020


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